tbuckley/cabot-search huggingface dataset:
Comparison of surgical outcomes and urinary functioning after phalloplasty with versus without urethral lengthening in transgender men
Authors: Freek P. W. de Rooij, Wouter B. van der Sluis, Brechje L. Ronkes, Thomas D. Steensma, Muhammed Al-Tamimi, R. Jeroen A. van Moorselaar, Mark-Bram Bouman, Garry L. S. Pigot
Journal: International Journal of Transgender Health (2022)

Background: Phalloplasty in transgender men is performed with or without Urethral Lengthening (UL). To create clear expectations in the choice of UL, an overview and comparison of outcomes is useful. Aims: To provide and compare surgical outcomes and urinary functioning after phalloplasty with versus without UL in transgender men. Methods: A single-center, retrospective chart review was conducted among transgender men who underwent phalloplasty with or without UL between 01-2013 and 10-2020. Primary outcomes were differences in complication and reoperation rates. Secondary outcomes were end-stages of voiding at last follow-up and differences in voiding analyses pre- and postoperatively. Results: Of 136 men, 91 (67%) underwent phalloplasty with, and 45 (33%) without UL. Wound infection (31 vs. 16%, p = 0.06) and partial flap loss (35 vs. 13%, p = 0.008) were predominately seen after UL. In the UL group, 43% urethral fistulas and 60% urethral strictures were observed, relative to one man without UL who had a urethral fistula (both p < 0.001). Meatal or perineal orifice stenosis was seen in 29% with versus 11% without UL (p = 0.02). Reoperation was needed in 81% with versus 27% without UL (p < 0.001). At follow-up, 80/91 (88%) after UL reached end-stage of voiding, with 60/80 (75%) able to void while standing and 20/80 (25%) having a definitive urethrostomy. The remaining 11/91 (12%) men were awaiting further treatment for urological complications. The men able to void while standing had a median of one reoperation (range 0-6), and a significant decrease in maximum flow rate on postoperative uroflowmetry (21.4 vs. 29.8 mL/s, p < 0.001). After phalloplasty without UL, all men had a definitive perineostomy without changes in voiding analyses. Discussion: The choice for or against UL during phalloplasty has become more relevant over the years. This comparison of surgical outcomes and urinary functioning can be useful in the shared decision-making process to come to the most suitable choice of phalloplasty.
An exploration of mental distress in transgender people in Ireland with reference to minority stress and dissonance theory
Authors: Jan M. A. de Vries, Carmel Downes, Danika Sharek, Louise Doyle, Rebecca Murphy, Thelma Begley, Edward McCann, Fintan Sheerin, Siobhán Smyth, Agnes Higgins
Journal: International Journal of Transgender Health (2022)

Introduction: Internationally mental distress is more prominent in the LGBTI community than the general population. The LGBTIreland study was set up to take stock of this in the Republic of Ireland. This paper reports on the analysis of the transgender group with reference to minority stress theory and cognitive dissonance theory. Method: An online survey was conducted addressing several aspects of mental health and distress that received responses from all groupings (n = 2,264) among which 12.3% (n = 279) identified as transgender. The survey consisted of several validated tools to measure depression, anxiety, stress (DASS-21), coping (CSES), self-esteem (RSES), alcohol and drugs misuse (AUDIT) and a variety of questions addressing demographics, experiential aspects, coping and self-related factors. Data analysis focused on predicting mental distress using DASS-general (composite of depression, anxiety and stress). Results: Transgender participants reported higher levels of mental distress, self-harm, suicidal ideation and attempts, and lower levels of self-esteem in comparison with the LGB groups, as well as the general population. Hierarchical multiple regression showed that 53% of variance in mental distress could be predicted from reduced self-esteem, the experience of harassment and not belonging in school. Furthermore, mental distress was highest among younger participants, those who were 'not out', those who had self-harmed and used avoidant coping. There was no significant difference in distress levels among those who had sought mental health support and those who had not. Conclusions: To understand mental distress in transgender people, the minority stress model is useful when taking into account both adverse external (environmental) and internal (cognitive/emotional) factors. The cognitive dissonance mechanism is essential in outlining the mechanism whereby gender incongruence is associated with psychological discomfort, low self-esteem and high mental distress.
A nationwide survey of individual family member experiences of youth gender dysphoria and diversity in Australia
Authors: Jason J. Westwater, Elizabeth A. Riley, Gregory M. Peterson
Journal: International Journal of Transgender Health (2022)

Previous research has highlighted that youth gender dysphoria (GD) and gender diversity (GDI) are experienced in unique ways by different family members, with youth outcomes significantly influenced by family support and understanding. Few studies on a national level have explored individual family member experiences, specifically family, social and healthcare experiences, involving young people, parent/carers and siblings.Using an online survey incorporating circular questioning, this study sought to discover individual family member experiences of youth GD/GDI in Australia, within a family, healthcare, and social context.Young people experiencing GD/GDI, parents/carers and siblings were recruited through Facebook advertising and completed an online survey, exploring positive and negative experiences of youth GD/GDI, within and outside of the family. Survey questions predominantly used Likert scales, with free-text fields, enabling both quantitative and qualitative data analysis.Six hundred and sixty young people aged 12-17 years experiencing GD/GDI, 158 parents/carers ranging in age from under 30 years to more than 60 years (most common age band was 40-49 years; 62%), and 40 siblings aged 12-17 years completed at least part of the online survey. Participants reported mixed experiences of youth GD/GDI with varying levels of understanding and support provided by family members and others. Parents and siblings generally felt it important for healthcare professionals to ask everyone's experience in the family, although only one-third of young people felt this was important. Most parents and young people also highlighted the importance of sibling support.The majority of young people felt misunderstood by other family members. Most family members, particularly young people, reported different viewpoints within families and primarily negative experiences. The research findings support sibling inclusion in healthcare appointments in certain circumstances, depending on context, and a whole of family approach overall, if agreeable to the family and unlikely to cause harm.
The Montréal Classification of urethral lengthening for phalloplasty in transmasculine patients—surgical techniques and urethral complications
Authors: Michelle Bonapace-Potvin, Elisabeth Lorange, Xiya Ma, Maria Cassandre Medor, Éric Bensimon, Pierre Brassard, Maud Bélanger
Journal: International Journal of Transgender Health (2022)

Phalloplasties are one of the most performed genital surgeries in the treatment of gender dysphoria for transmasculine patients. Urethral lengthening is an essential component of phalloplasties. Few techniques have been described for the creation of this pars fixa urethra. The purpose of this article is to present the Montréal Classification for pars fixa urethral lengthening, to detail the surgical techniques and to report on clinical outcomes.All patients undergoing phalloplasty from November 2016 to February 2019 were included in this study. Patient demographics, type of surgery and urological complications were recorded. Statistics were performed using student's T-test, Chi-squared test, Fisher's exact test and One-way ANOVA. Patients underwent either type 1, type 2, or type 3 urethral reconstruction.Of the 84 total patients, 45 underwent type 1 lengthening, 28 type 2, and 11 type 3. Eighteen and 33 patients underwent single-stage and two stage anastomosis of the pars fixa to the pars pendulans neourethra, respectively. Thirty-three patients have not had any additional surgeries to date. Post-operative urological complications for immediate anastomosis and two-stage anastomosis were reported in 77.7% and 18.2% of patients, respectively.We propose a classification as well as a description of three types of urethral lengthening techniques. Over the last few years, we have shifted away from single-stage anastomosis and have adopted a two-stage anastomosis technique. Our experience allows us to classify urethral lengthening and to standardize care depending on patient characteristics, leading to excellent results.
Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy
Authors: Yi Wang, Kai Conrad Cecil Johnson, Margaret E. Gatti-Mays, Zihai Li
Journal: Journal of Hematology & Oncology (2022)

Immune checkpoint inhibitors targeting programmed cell death protein 1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated protein 4 provide deep and durable treatment responses which have revolutionized oncology. However, despite over 40% of cancer patients being eligible to receive immunotherapy, only 12% of patients gain benefit. A key to understanding what differentiates treatment response from non-response is better defining the role of the innate immune system in anti-tumor immunity and immune tolerance. Teleologically, myeloid cells, including macrophages, dendritic cells, monocytes, and neutrophils, initiate a response to invading pathogens and tissue repair after pathogen clearance is successfully accomplished. However, in the tumor microenvironment (TME), these innate cells are hijacked by the tumor cells and are imprinted to furthering tumor propagation and dissemination. Major advancements have been made in the field, especially related to the heterogeneity of myeloid cells and their function in the TME at the single cell level, a topic that has been highlighted by several recent international meetings including the 2021 China Cancer Immunotherapy workshop in Beijing. Here, we provide an up-to-date summary of the mechanisms by which major myeloid cells in the TME facilitate immunosuppression, enable tumor growth, foster tumor plasticity, and confer therapeutic resistance. We discuss ongoing strategies targeting the myeloid compartment in the preclinical and clinical settings which include: (1) altering myeloid cell composition within the TME; (2) functional blockade of immune-suppressive myeloid cells; (3) reprogramming myeloid cells to acquire pro-inflammatory properties; (4) modulating myeloid cells via cytokines; (5) myeloid cell therapies; and (6) emerging targets such as Siglec-15, TREM2, MARCO, LILRB2, and CLEVER-1. There is a significant promise that myeloid cell-based immunotherapy will help advance immuno-oncology in years to come.
Immune Response to SARS-CoV-2 Infection in Children
Authors: C. Mary Healy
Journal: JAMA Pediatrics (2022)

Chee Fu Yung, MBChB; Seyed Ehsan Saffari, PhD; Shirley Yun Yan Mah, BSc; Natalie Woon Hui Tan, MBBS; Wan-Ni Chia, PhD; Koh Cheng Thoon, MBBS; Lin-Fa Wang, PhD
Transcriptional regulation of the thymus master regulator <i>Foxn1</i>
Authors: Noam Kadouri, Tal Givony, Shir Nevo, Joschka Hey, Shifra Ben Dor, Golda Damari, Bareket Dassa, Jan Dobes, Dieter Weichenhan, Marion Bähr, Michelle Paulsen, Rebecca Haffner-Krausz, Marcus A. Mall, Christoph Plass, Yael Goldfarb, Jakub Abramson
Journal: Science Immunology (2022)

FOXN1 is a transcription factor critical for the development of both thymic epithelial cell (TEC) and hair follicle cell (HFC) compartments. However, mechanisms controlling its expression remain poorly understood. To address this question, we performed thorough analyses of the evolutionary conservation and chromatin status of the Foxn1 locus in different tissues and states and identified several putative cis-regulatory regions unique to TECs versus HFCs. Furthermore, experiments using genetically modified mice with specific deletions in the Foxn1 locus and additional bioinformatic analyses helped us identify key regions and transcription factors involved in either positive or negative regulation of Foxn1 in both TECs and HFCs. Specifically, we identified SIX1 and FOXN1 itself as key factors inducing Foxn1 expression in embryonic and neonatal TECs. Together, our data provide important mechanistic insights into the transcriptional regulation of the Foxn1 gene in TEC versus HFC and highlight the role of FOXN1 in its autoregulation.
Could the new BA.2.75 sub-variant lead to another COVID-19 wave in the world? – Correspondence
Authors: Nour Shaheen, Abdelrahman Mohamed, Youssef Soliman, Omar Ahmed Abdelwahab, Rehab Adel Diab, Mariam Tarek Desouki, Ala’ Abdala Rababah, Abdulrhman Khaity, Mahmoud Tarek Hefnawy, Sarya Swed, Ahmed Shaheen, Bahaa Elfakharany, Sheikh Shoib
Journal: International Journal of Surgery (2022)
Dynamic Spatial-Temporal Expression Ratio of X Chromosome to Autosomes But Stable Dosage Compensation in Mammals
Authors: Sheng Hu Qian, Yu-Li Xiong, Lu Chen, Ying-Jie Geng, Xiao-Man Tang, Zhen-Xia Chen
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract In the evolutionary model of dosage compensation, per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males (XY) compared to females (XX). However, the expression regulation of X-linked genes is still controversial, and comprehensive evaluations are still lacking. By integrating multi-omics datasets in mammals, we investigated the expression ratios including X to autosomes (X:AA ratio) and X to orthologs (X:XX ratio) at the transcriptome, translatome, and proteome levels. We revealed a dynamic spatial-temporal X:AA ratio during development in humans and mice. Meanwhile, by tracing the evolution of orthologous gene expression in chickens, platypuses, and opossums, we found a stable expression ratio of X-linked genes in humans to their autosomal orthologs in other species (X:XX ≈ 1) across tissues and developmental stages, demonstrating stable dosage compensation in mammals. We also found that different epigenetic regulations contributed to the high tissue specificity and stage specificity of X-linked gene expression, thus affecting X:AA ratios. It could be concluded that the dynamics of X:AA ratios were attributed to the different gene contents and expression preferences of the X chromosome, rather than the stable dosage compensation.
Efficacy and Safety of an Extravascular Implantable Cardioverter–Defibrillator
Authors: Paul Friedman, Francis Murgatroyd, Lucas V.A. Boersma, Jaimie Manlucu, David O’Donnell, Bradley P. Knight, Nicolas Clémenty, Christophe Leclercq, Anish Amin, Béla P. Merkely, Ulrika M. Birgersdotter-Green, Joseph Y.S. Chan, Mauro Biffi, Reinoud E. Knops, Greg Engel, Ignacio Muñoz Carvajal, Laurence M. Epstein, Venkata Sagi, Jens B. Johansen, Maciej Sterliński, Clemens Steinwender, Troy Hounshell, Richard Abben, Amy E. Thompson, Christopher Wiggenhorn, Sarah Willey, Ian Crozier
Journal: New England Journal of Medicine (2022)

The extravascular implantable cardioverter–defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known.
Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response
Authors: Hanna E. Persha, Shumei Kato, Pradip De, Jacob J. Adashek, Jason K. Sicklick, Vivek Subbiah, Razelle Kurzrock
Journal: Journal of Hematology & Oncology (2022)

Abstract There is a paucity of information about molecularly driven therapy in osteosarcomas. We report a 31-year-old woman with chemotherapy–refractory metastatic osteosarcoma who was successfully treated with the combination of palbociclib (CDK4/6 inhibitor) and lenvatinib (multikinase FGFR inhibitor), selected based on next generation sequencing that showed CDK4 and CCND2 amplifications (upregulates CDK4/6), and FGF6 (ligand for FGFR1,2 and 4), FGF23 (ligand for FGFR1,2,3, and 4) and FRS2 (adaptor protein for FGFR signaling) amplifications. The patient’s tumor showed 68% reduction in positron emission tomography (PET) avidity, lasting 31 months after therapy initiation, when a solitary recurrence occurred, was resected, and treatment continued. The patient remains on matched targeted therapy at 51 + months from the start of the combination. Treatment was given at reduced dosing (lenvatinib 10 mg oral daily (approved dose = 24 mg daily)) and palbociclib 75 mg oral daily, one week on and one week off (approved dose = 125 mg oral daily, three weeks on/one week off) and is tolerated well. Therefore, co-targeting the aberrant cyclin and FGFR pathways resulted in long-term exceptional response in a patient with refractory advanced osteosarcoma.
Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit
Authors: Emily Pei-Ying Lin, Chih-Yuan Hsu, Jeng-Fong Chiou, Lynne Berry, Leora Horn, Paul Bunn, James Chih-Hsin Yang, Pan-Chyr Yang, Alex A. Adjei, Yu Shyr
Journal: Journal of Thoracic Oncology (2022)
An update on Epstein-Barr virus–and human T-lymphotropic virus type-1–induced cutaneous manifestations. CME Part II
Authors: Alejandro A. Gru, Jose A. Plaza, Jose A. Sanches, Denis Miyashiro, Omar P. Sangueza, Francisco Bravo Puccio, Sonia Toussaint, J. Martin Sangueza
Journal: Journal of the American Academy of Dermatology (2022)
A Knock-In Mouse Model of Thymoma With the GTF2I L424H Mutation
Authors: Yongfeng He, In-Kyu Kim, Jing Bian, Alexander Polyzos, Dafne Campigli Di Giammartino, Yu-Wen Zhang, Ji Luo, Maria O. Hernandez, Noemi Kedei, Maggie Cam, Alain C. Borczuk, Trevor Lee, Yumin Han, Elizabeth A. Conner, Madeline Wong, Desiree C. Tillo, Shigeki Umemura, Vincent Chen, Lydia Ruan, Jessica B. White, Ileana C. Miranda, Parirokh P. Awasthi, Nasser K. Altorki, Prajan Divakar, Olivier Elemento, Effie Apostolou, Giuseppe Giaccone
Journal: Journal of Thoracic Oncology (2022)
IL-6/STAT3 axis dictates the PNPLA3-mediated susceptibility to non-alcoholic fatty liver disease
Authors: Jiwoon Park, Yuanyuan Zhao, Fan Zhang, Shaoyan Zhang, Andrew C. Kwong, Yujie Zhang, Hans-Heinrich Hoffmann, Leila Bushweller, Xin Wu, Alison W. Ashbrook, Branko Stefanovic, Shuyang Chen, Andrea D. Branch, Christopher E. Mason, Jae U. Jung, Charles M. Rice, Xianfang Wu
Journal: Journal of Hepatology (2022)
Inhibition of the chemokine signal regulator FROUNT by disulfiram ameliorates crescentic glomerulonephritis
Authors: Etsuko Toda, Anri Sawada, Kazuhiro Takeuchi, Kyoko Wakamatsu, Arimi Ishikawa, Naomi Kuwahara, Yurika Sawa, Saeko Hatanaka, Kana Kokubo, Kosho Makino, Hideyo Takahashi, Yoko Endo, Shinobu Kunugi, Mika Terasaki, Yasuhiro Terasaki, Kouji Matsushima, Yuya Terashima, Akira Shimizu
Journal: Kidney International (2022)

Activated monocytes/macrophages promote glomerular injury, including crescent formation, in anti-glomerular basement membrane (GBM) glomerulonephritis. Disulfiram, an alcohol-aversion drug, inhibits monocyte/macrophage migration by inhibiting FROUNT, a cytosolic protein that enhances chemokine receptor signaling. Our study found that disulfiram at a human equivalent dose successfully blocked albuminuria and crescent formation with podocyte loss, and later stage kidney fibrotic lesions, in a rat model of anti-GBM glomerulonephritis. A disulfiram derivative, DSF-41, with more potent FROUNT inhibition activity, inhibited glomerulonephritis at a lower dose than disulfiram. Disulfiram markedly reduced the number of monocytes or macrophages at the early stage of glomerulonephritis and that of CD3+ and CD8+ lymphocytes at the established stage. Impaired pseudopodia formation was observed in the glomerular monocytes/macrophages of the disulfiram group; consistent with the in vitro observation that disulfiram blocked chemokine-dependent pseudopodia formation and chemotaxis of bone marrow-derived monocytes/macrophages. Furthermore, disulfiram suppressed macrophage activation as revealed by reduced expression of inflammatory cytokines and chemokines (TNF-α, CCL2, and CXCL9) and reduced CD86 and MHC class II expressions in monocytes/macrophages during glomerulonephritis. The dramatic reduction in monocyte/macrophage number might have resulted from disulfiram suppression of both the chemotactic response of monocytes/macrophages and their subsequent activation to produce cytokines and chemokines, which further recruit monocytes. Additionally, FROUNT was expressed in CD68+ monocytes/macrophages infiltrating the crescentic glomeruli in human anti-GBM glomerulonephritis. Thus, disulfiram can be a highly effective and safe drug for the treatment of glomerulonephritis by blocking the chemotactic responses of monocytes/macrophages and their activation status in the glomerulus.
Improving the reporting of allergic adverse events during immunotherapy for food allergy
Authors: Paul J. Turner, Nandinee Patel, Mika J. Mäkelä, Kaarina Kukkonen, Antoine Deschildre, Katharina Blumchen, Pablo Rodríguez del Río, Montserrat Fernández-Rivas, Montserrat Alvaro-Lozano, Kirsten Beyer
Journal: Journal of Allergy and Clinical Immunology (2022)
Identification of mast cell progenitor cells in the airways of individuals with allergic asthma
Authors: Ryan C. Murphy, Yu‐Hua Chow, Ying Lai, Taha Al‐Shaikhly, Daniel H. Petroni, Michele Black, Jessica A. Hamerman, Adam Lacy‐Hulbert, Adrian M. Piliponsky, Teal S. Hallstrand
Journal: Allergy (2022)
Graduate Medical Education
Journal: JAMA (1992)

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CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011
Authors: Q. T. Ostrom, H. Gittleman, P. Liao, C. Rouse, Y. Chen, J. Dowling, Y. Wolinsky, C. Kruchko, J. Barnholtz-Sloan
Journal: Neuro-Oncology (2014)